Restoring an erection
Researchers from the Albert Einstein College of Medicine have developed a topical drug that regenerates and restores the function of cavernous nerves damaged by radical prostatectomy – the most common method of treating prostate cancer. The drug was successfully tested on rats.
Radical prostatectomy is considered the main method of treatment of localized prostate cancer.
Despite the appearance of neuropreserving techniques, radical prostatectomy is often accompanied by damage to the cavernous nerves – parasympathetic fibers that control erectile function, regulating blood flow to the penis. According to researchers, about 60% of patients report having erectile dysfunction 18 months after surgery, and only less than 30% have an erection sufficient for sexual intercourse after five years. Viagra and other drugs to restore potency in these patients are rarely effective.
Ten years ago, Dr. David Sharp and his colleagues discovered that the enzyme FL2 (fidgetin-like 2) inhibits the migration of skin cells to damage in order to heal them. To speed up wound healing, the researchers developed FL2 antagonists – short interfering RNA (siRNA) molecules that inhibit the gene encoding FL2. Packed in nanoparticles and sprayed onto the skin of mice, siRNA not only healed wounds twice as fast as without treatment, but also repaired damaged tissues. A study conducted in February 2021 on rats showed that siRNA also contributed to the healing of chemical burns of the cornea.
Sharp and colleagues suggested that damaged nerves may be particularly susceptible to this drug: for unknown reasons, the FL2 gene becomes overactive after nerve cells are damaged, causing cells to produce copious amounts of the enzyme of the same name.
The researchers tested the drug on rat models of peripheral nerve damage, in which the cavernous nerves were either compressed or torn, simulating damage during radical prostatectomy. The siRNA gel was applied to the nerves immediately after the injury.
With nerve compression, siRNA treatment enhanced the regeneration of nerve fibers and restored function: this was shown using cavernometry, a test in which pressure inside the penis was measured after electrical stimulation of cavernous nerves. Three and four weeks after therapy, the animals showed significantly better erectile function compared to the control group. A month later, the data of the cavernometry of the rats of the experimental group was comparable with the data obtained from healthy animals.
After complete nerve rupture, the use of siRNA also caused regeneration of nerve fibers and partial restoration of erectile function. Regenerated nerves were found in 7 of the 8 treated and none of the control animals. The siRNA drug was able to repair ruptures several millimeters long – an amazing result, previously achieved only with the help of nerve transplantation.
Neurons cultured in Petri dishes and treated with either a control (inactive) composition (left) or a FL2 siRNA preparation (right). siRNA contribute to the restoration of long processes (axons).
The researchers also found that after treatment with siRNA, the penile cavernous bodies contained higher levels of nitric oxide synthase (NO-synthase) compared to controls. This enzyme produces nitric oxide, which is necessary to trigger a cascade of reactions leading to an erection. Viagra and similar drugs are not effective in the absence of nitric oxide, so at least a slight increase in its level will allow you to restore potency with known approved drugs.
The research team is currently investigating whether siRNAs can promote nerve regeneration after spinal cord injuries.
Article by L.Baker et al. Fidgetin-like 2 negatively regulates axonal growth and can be targeted to promote functional nerve regeneration published in JCI Insight.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on the materials of Albert Einstein College of Medicine: Einstein Researchers Develop Novel Drug That Regenerates Erectile Nerves Damaged by Prostate Surgery.